The long term goal of our research is to design complex biomaterial scaffolds that can mimic the micro- architecture of cardiac tissues and to augment regeneration therapies. These tissue-like structures will have the appropriate microarchitectural features of native tissues including a functioning vasculature. To fabricate these tissues we are interested in using natural molecules such as hyaluronic acid (HA; also called hyaluronan)-based biomaterials, because of the ubiquitous presence of HA in the extracellular matrix (ECM) of tissues and the significant role that HA inherently plays in wound healing. The objective of the proposed research is to develop methods to create 3D scaffolds of native ECM components with complex internal architecture and cell encapsulation. To fabricate such scaffolds, we will develop an innovative direct-write platform based on a projection-style stereolithographic (SL) method, coined as PSL. In Specific Aim 1, we will develop and optimize the PSL system for the fabrication of 3D microstructures using HA with Arg-Gly-Asp (RGD) and matrix metalloproteinase (MMP). In Specific Aim 2, we will use PSL for Direct-write 3D HA scaffolds encapsulating cardiomyocytes. In Specific Aim 3, we will create vascularized structures in a 3D scaffold and analyze vasculature functions. We will seed an endothelial cell lining within microchannels. The seeding process will be optimized by adjusting the cell seeding density and duration as well as surface chemistry. The vascular function and biomechanical properties of these engineered tissue constructs will be determined in vitro. PUBLIC HEALTH RELEVANCE: This project seeks to develop a novel biofabrication platform to create three-dimensional (3D) scaffolds of native extracellular matrix components with complex internal architectures and cell encapsulation. The goal of the project is to create vascularized structures in the 3D scaffolds